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Biomedical subjects

F O'Brien

Publications and source records attributed to F O'Brien.

At least 37 records · Page 2Linked to original sources
PubMed1998

Assessment by nasal biopsy of long-term use of mometasone furoate aqueous nasal spray (Nasonex) in the treatment of perennial rhinitis.

Allergic rhinitis is associated with specific histopathologic changes in the nasal mucosa including squamous metaplasia and local eosinophilia. Previous studies have shown that mometasone furoate aqueous nasal spray is effective and well tolerated in reducing perennial rhinitis and seasonal allergic rhinitis symptoms. We undertook a multicenter, open-label study to evaluate, by nasal biopsy, the tissue changes associated with mometasone furoate use (200 microg/day) during a 12-month treatment period in patients with perennial rhinitis. Of the 69 patients enrolled in the study, 52 completed all 12 months of treatment. Nasal biopsy specimens obtained from patients at baseline and after treatment were evaluated in a blinded fashion by computerized image analysis, qualitative histologic examination, and immunocytochemistry. Morphologic examination of nasal biopsy specimens showed a decrease in focal metaplasia, no change in epithelial thickness, and no sign of atrophy after treatment with mometasone furoate. Immunocytochemical analyses of nasal biopsy specimens obtained before and after treatment revealed a significant decrease in major basic protein-positive eosinophils and tryptase-positive mast cells in the epithelium and lamina propria after treatment. Mometasone furoate appeared to attenuate the inflammatory process by reducing the extent of inflammatory cell infiltration, particularly of eosinophils. This study demonstrated that long-term administration of mometasone furoate is not associated with adverse tissue changes in the nasal mucosa of patients with perennial rhinitis.

Administration, Intranasal↗
PubMed1998

Thirteen-year follow-up of deliberate self-harm, using linked data.

BACKGROUND: We describe a national cohort of individuals surviving an episode of deliberate self-harm (DSH). Subsequent admissions for DSH and mortality over the following 13 years were studied. METHOD: In 1981, 8304 individuals were discharged from Scottish general hospitals with a diagnosis of attempted suicide (E950-959). They were followed-up to the end of 1994 using the Scottish Linked Data Set. Mortality was compared to the Scottish population using person-years analysis. RESULTS: 2624 people (31.6%) were readmitted with further episodes of DSH. The median number of readmissions was 1, range 1-137. The observed:expected ratio for all-cause mortality was 2.26 (95% CI 2.13-2.26). One hundred and sixty-eight people (2%) died from suicide, and 46 (0.6%) from undetermined causes. The observed:expected ratio for suicide plus undetermined deaths was 12.17 (95% CI 10.64-13.91). Accidental deaths in men and homicide deaths in men and women were elevated. The pattern of deaths from other causes suggested that alcohol misuse was a contributory factor. CONCLUSIONS: People admitted to general hospitals in Scotland after attempted suicide are at high risk of readmission for further episodes of DSH. Long-term follow-up of such large cohorts is impractical, but services should review the scope for intervention in alcohol misuse following DSH.

Adolescent↗
PubMed1997

Enhanced expression of high-affinity IgE receptor (Fc epsilon RI) alpha chain in human allergen-induced rhinitis with co-localization to mast cells, macrophages, eosinophils, and dendritic cells.

BACKGROUND: IgE-dependent activation of mast cells and basophils through the high-affinity IgE receptor (Fc epsilon RI) is involved in the pathogenesis of allergen-induced immediate and late responses. OBJECTIVE: We investigated the expression and cellular distribution of Fc epsilon RI in the nasal mucosa after allergen challenge in patients with summer hay fever. METHODS: Fourteen grass pollen-sensitive patients and seven normal control subjects underwent nasal challenge with grass pollen and allergen diluent in random order separated by 2 weeks. Nasal airway caliber was monitored by acoustic rhinometry, and nasal biopsy was performed at 6 hours. Messenger RNA for Fc epsilon RI was determined by using reverse-transcription polymerase chain reaction, and Fc epsilon RI protein expression was determined by immunohistology with a mouse monoclonal antibody (22E7) and a rabbit polyclonal antibody (997) directed against the alpha subunit. Co-localization of Fc epsilon RI receptors was performed by using double-immunostaining methods. RESULTS: In atopic subjects, there was a significant early decrease in nasal airway caliber, which extended up to 6 hours after allergen challenge. Fc epsilon RI mRNA levels were elevated at 6 hours (p = 0.03). Cells expressing Fc epsilon RI protein were increased in patients with atopic rhinitis compared with normal control subjects (p = 0.03). Further increases in Fc epsilon RI+ cells were observed after allergen challenge only in the atopic group (p = 0.02). Double immunohistochemistry revealed that the majority of Fc epsilon RI+ cells were mast cells (64%), followed by macrophages (20%), eosinophils (4%), and dendritic cells (2%), with 10% Fc epsilon RI+ cells being unidentified. CONCLUSIONS: Our results demonstrate increased Fc epsilon RI expression during allergen-induced rhinitis and highlight a potential target for treatment.

Adult↗
PubMed1997

IL-5 production by allergen-stimulated T cells following grass pollen immunotherapy for seasonal allergic rhinitis.

Grass pollen immunotherapy for the treatment of seasonal allergic rhinitis ('summer hayfever') results in improvement in symptoms, a reduction in the early and late phase responses to allergen provocation and decreased tissue eosinophilia. Immunotherapy may act by altering the pattern of cytokine production by allergen-specific T cells from a 'Th2-type' (IL-4 and IL-5) profile to a 'Th1-type' (interferon-gamma (IFN-gamma)) profile. We set out to determine whether clinical improvement following specific allergen immunotherapy is accompanied by reduced production of the pro-eosinophilic and archetypal 'Th2-type' cytokine, IL-5. Peripheral blood mononuclear cells (PBMC) were isolated from (i) 13 patients who had received 6 or 7 years' continuous conventional immunotherapy with timothy grass pollen (Phleum pratense); (ii) 14 patients who had received 3 or 4 years of conventional immunotherapy followed by 3 years of placebo treatment; (iii) 12 matched seasonal rhinitic patients who had never received immunotherapy; and (iv) 17 non-atopic normal controls. PBMC were stimulated with 20 microg/ml and 200 microg/ml P. pratense extract, or 10 microg/ml of Mycobacterium tuberculosis purified protein derivative (PPD), at 2 x 10(6) cells/ml and 5 x 10(6) cells/ml. IL-5 concentrations in culture supernatants collected after 6 days' culture were measured by ELISA. IL-5 production in response to stimulation with P. pratense extract was highly reproducible and was elevated in both of the immunotherapy treated groups and the untreated rhinitics relative to non-atopic controls (P<0.005 for each group relative to non-atopic controls, under each of the four conditions tested). However, no significant reduction was observed in IL-5 production when immunotherapy treated patients were compared with untreated rhinitic controls. Moreover, abrogation of the cutaneous late-phase responses to allergen following treatment was not associated with reduced IL-5 production by allergen-stimulated peripheral blood T cells. Reduced IL-5 production by peripheral blood T cells may not be necessary for immunotherapy to be effective. Local immunodulation of T cell responses may play a role in this form of treatment.

Adult↗
PubMed1997

Suicide in the 12 months after discharge from psychiatric inpatient care, Scotland 1968-92.

STUDY OBJECTIVE: To investigate the rate of suicide in the 12 months after discharge from psychiatric hospital and to determine its relationship to age, diagnosis, and period. DESIGN: Cohort study of patients discharged from psychiatric hospital. SETTING: Scotland. PARTICIPANTS: Altogether 159,742 men and 178,271 women, aged 15-84, who were discharged from Scottish psychiatric hospitals during 1968-92. MAIN RESULTS: During the 25 year period, 1212 male patients committed suicide in 198,059 person years at risk (612 per 100,000; 95% confidence interval (CI) 578,647) and 1099 female patients committed suicide in 228,993 person years at risk (480 per 100,000; 95% CI 452, 509). The overall standardised mortality ratio (general population rate = 1) was 27 (95% CI 26, 29) in men and 40 (95% CI 38, 43) in women. There were variations in the suicide rates in relation to age, diagnosis, and period. The ratio of the 1-28 day rate to the rate between days 29 and 365 over the whole study period was 1.7 (95% CI 1.4, 1.9) in men and 1.6 (95% CI 1.3, 1.8) in women. CONCLUSIONS: The variations in the post discharge suicide rate by age, sex, diagnosis, geographical location, and period suggest that there are several risk factors which vary in their distribution. Further study of these may lead to the development of effective interventions.

Adolescent↗
PubMed1997

RANTES in human allergen-induced rhinitis: cellular source and relation to tissue eosinophilia.

Human allergen-induced rhinitis is associated with recruitment and activation of CD4+ T lymphocytes and eosinophils. RANTES is a novel CC chemokine that is a potent chemoattractant for both memory T cells and eosinophils. We therefore investigated RANTES in the nasal mucosa after local allergen provocation. Nasal lavage was performed, and biopsies from the inferior nasal turbinate were taken from 14 atopic, seasonal rhinitic patients and seven normal subjects for as long as 6 h after challenge with a grass pollen extract and after a control (allergen diluent) challenge. In five of seven rhinitics tested, radioimmunoassay of nasal fluid demonstrated increases in RANTES at 2 to 4 h (p < 0.05). Nasal allergen challenge provoked significant increases in RANTES mRNA (p = 0.0015) and protein (p = 0.01) containing cells in the nasal submucosa at 6 h. No changes were observed in normal subjects. Increases in RANTES mRNA+ cells correlated with the associated increases in eosinophils (r = 0.78, p = 0.001). Colocalization studies revealed that the majority of RANTES mRNA+ cells were macrophages (51%) followed by eosinophils (15%), T lymphocytes (11%), and mast cells (3%). Our results demonstrate that allergen-induced rhinitis is associated with release of RANTES and upregulation of RANTES mRNA and protein+ cells, predominantly macrophages, in the nasal mucosa. RANTES synthesis, release, or receptor antagonism may represent a potential target for antiallergy treatment.

Adult↗
PubMed1996

Paravertebral block for breast cancer surgery.

PURPOSE: Major breast cancer surgery is associated with a high incidence of postoperative nausea, vomiting and pain. Regional anaesthesia, with intraoperative sedation, would seem an ideal alternative to general anaesthesia for this type of surgery. We report our initial experience using paravertebral blocks (PVB) to provide anaesthesia for major breast surgery. METHODS: Twenty-five patients agreeing to have surgery performed under paravertebral blocks were studied. Procedures performed varied from simple lumpectomy with axillary dissection to modified radical mastectomy with axillary dissection. During monitored sedation, blocks opposite spinous processes of C7-T6 were performed using bupivacaine 0.5% with epinephrine, 3-4 ml per segment. Patients were evaluated for 72 hr and were requested to document: (i) when sensation returned (ii) incidence and frequency of nausea or vomiting (iii) degree of discomfort and medication taken. RESULTS: Twenty patients had blocks that required no supplementation. Five patients had blocks that were incomplete. No complications were attributed to the blocks. Post-operatively, patients with successful blocks had minimal nausea, vomiting and pain. No patients found the procedure unsatisfactory. Patients with successful blocks were all very satisfied. CONCLUSION: Our initial results show that PVB for breast cancer surgery can be successfully performed in a majority of patients with few side effects. All patients with successful blocks were returned to the ambulatory care unit, bypassing the recovery room. That breast cancer surgery under regional anaesthesia can be safely performed as an ambulatory procedure has the potential for accomplishing major cost-saving.

Adult↗
PubMed1995

Heterosexual transmission of HIV analysed by generalized estimating equations.

A longitudinal analysis of a partner study is compared with a cross-sectional analysis which identify behavioural and biological risk factors for heterosexual transmission of HIV. Using generalized estimating equations (GEEs) a random effects logistic model is used for the longitudinal analysis. These approaches are illustrated by the Edinburgh heterosexual partner study. The longitudinal analysis finds that 'high-risk' sexual practices, unprotected intercourse for HIV and a low CD4 count in the index case significantly increase the risk of HIV transmission. The cross-sectional analysis, however, only indicates 'high-risk' sexual practices as favourable for HIV transmission.

Adolescent↗
PubMed1995

Micrometastases in bone marrow of patients undergoing "curative" surgery for gastrointestinal cancer.

BACKGROUND & AIMS: Immunohistochemical detection of bone marrow micrometastases has been reported as a prognostic marker in colorectal cancer. The aims of this study were to evaluate the potential advantage of flow cytometry as an objective method of identifying and quantifying micrometastatic deposits within bone marrow and to determine the prevalence and quantity of micrometastases in patients undergoing surgery for gastrointestinal cancers. METHODS: Flow cytometry was first validated by a controlled "spike" experiment in which varying numbers of neoplastic epithelial cells were added to bone marrow, and cytometry was performed in a blinded fashion. Three neoplastic cell lines (colonic and esophageal) with varying degrees of expression of cytokeratin-18 were used. Epithelial cells were detected by dual staining with fluorescence-labeled, monoclonal anti-cytokeratin, and propidium iodide. RESULTS: Cytometry reproducibly detected the presence of > or = 10 neoplastic cells per 10(5) marrow cells. Micrometastases were found in 20%-30% of patients undergoing potentially curative resection of colorectal and gastroesophageal adenocarcinomas. There was a trend toward increasing positivity for marrow deposits with advanced Dukes' staging of colorectal cancer. CONCLUSIONS: Flow cytometric assessment of bone marrow is a reliable, objective, and quantitative method of detecting micrometastatic deposits found in a substantial subset of patients undergoing surgery for gastrointestinal adenocarcinomas.

Adenocarcinoma↗
PubMed1995

HIV prevalence and risk factors in university students.

OBJECTIVE: To estimate HIV prevalence and risks in university students. DESIGN: Anonymous self-completion questionnaire and HIV survey with saliva samples. SETTING: University students at matriculation. PARTICIPANTS: All first and third year undergraduates and newly registering postgraduates at the University of Edinburgh, Scotland. MAIN OUTCOME MEASURES: HIV prevalence, sexual behaviour, condom use, drug use. RESULTS: The questionnaire responses were used to classify the 4665 respondents into four groups, ordered by risk of HIV positivity, and a sample of 2041 was selected for testing. All of the top two risk groups were tested (217 and 758 tests, respectively) as well as a random sample of the others. Five positive HIV-antibody tests were detected, all from the highest risk group. This gives an estimated rate of 1.2 per 1000 (95% confidence interval, 0.4-2.9) for all respondents. Only one of the five HIV-positives had been tested for HIV. The factors associated with HIV positivity were residence in Africa, intravenous drug use and male homosexuality. Overall, 74% of respondents reported ever having had sexual intercourse and this rate was the same for men and women. Reported intravenous drug use was very low: 0.5% for men and 0.1% for women. Condom use was more common for partners of short acquaintance, but unrelated to the number of sexual partners in the last year. CONCLUSIONS: There was no evidence of the spread of HIV infection beyond known high-risk groups in this population. This may be a result of relatively low levels of HIV risk-taking behaviour in the majority of respondents.

Adult↗
PubMed1994

Death from malignant disease after surgery for duodenal ulcer.

A total of 2241 patients who had an operation for duodenal ulcer between 1947 and 1968 were followed up to determine the cause of death and to compare the observed number of deaths with the expected. Death certificates were traced for 1251 of 1387 known to have died. Observed deaths from all causes were significantly greater than expected (O/E 1.13) (95% CI 1.08 to 1.20). This was because of significant increases in deaths from neoplasms (O/E 1.25) (95% CI 1.13 to 1.39) and digestive diseases (O/E 1.71) (95% CI 1.11 to 2.59). Analysis of deaths from malignant disease showed an excess of deaths from carcinoma of lung (O/E 1.37) (95% CI 1.14 to 1.62) and from smoking related cancers (O/E 1.32) (95% CI 1.13 to 1.52) but there was no significant excess mortality from any other neoplasm. An excess of deaths within one year of the operation was seen from circulatory disease (O/E 1.85) (95% CI 1.17 to 2.78), respiratory disease (O/E 3.56) (95% CI 1.78 to 6.37), and digestive disease (O/E 21.46) (95% CI 13.75 to 31.93). These deaths are concentrated in the first postoperative month and as there is no excess mortality from circulatory, respiratory or digestive disease between 1 and 20 years postoperatively, show the direct effects of the operation as a cause of death. This together with the excess mortality from all respiratory disease confirms that excess mortality after duodenal ulcer surgery is, in the short term, the result of the operation itself and in the long term largely attributable to cigarette smoking. Operations for gastric ulcer largely account for the subsequent excess mortality from gastric cancer reported after peptic ulcer surgery. The findings do not support the theory that the operation has carcinogenic effects and do not support the case for routine endoscopic screening after operations for duodenal ulcer.

Adult↗
PubMed1993

Rural population mixing and childhood leukaemia: effects of the North Sea oil industry in Scotland, including the area near Dounreay nuclear site.

OBJECTIVE: To determine if any excess of childhood leukaemia and non-Hodgkin's lymphoma was associated with certain striking examples of population mixing in rural Scotland produced by the North Sea oil industry. DESIGN: Details were traced for over 30,000 workers involved in the construction of the large oil terminals in the Shetland and Orkney islands in northern Scotland or employed offshore. Home addresses of the 17,160 Scottish residents were postcoded, integrated with census data, and then classified as urban or rural. Rural postcode sectors, ranked by proportion of oil workers, were grouped into three categories with similar numbers of children but contrasting densities of oil workers. The incidence of leukaemia and non-Hodgkin's lymphoma was examined in these rural (and also in urban) categories in the periods 1974-8, 1979-83 and 1984-8. SETTING: Scotland. SUBJECTS: Young people below age 25. RESULTS: A significant excess of leukaemia and non-Hodgkin's lymphoma was found in 1979-83 in the group of rural home areas with the largest proportion of oil workers, following closely on large increases in the workforce. The area near the Dounreay nuclear installation, where an excess of leukaemia is already well known, was within the rural high oil category. CONCLUSION: The findings support the infection hypothesis that population mixing can increase the incidence of childhood leukaemia in rural areas. They also suggest that the recent excess in the Dounreay-Thurso area is due to population mixing linked to the oil industry, promoted by certain unusual local demographic factors.

Adolescent↗